Evaluating mechanisms of environmental chemical exposure with developing zebrafish urinary system
Many children with improper organ growth before birth have
disfigured pelvic organs. In many cases these disfigured organs affect the
urinary system: they urinate from more than one hole, their kidneys are
blocked, or their bladder is on the outside of their body. Urinary organs must
grow properly before birth in order to function and children with improper
organ growth face a lifetime of medical procedures, surgery, and doctor’s
visits. There is concerning evidence that chemicals in our environment can affect
how urinary organs grow. How these chemicals disrupt organ growth is unclear.
Zebrafish are frequently used to study such disruptions, but were not thought
to have the same urinary organs as humans. Our lab looked closely at zebrafish
and discovered they have bladders that hold urine, contract, and even have
similar cells to human bladders. This allows us to study how zebrafish bladders
grow and change, test what happens to genes when zebrafish are exposed to
specific chemicals, and ask questions about the DNA-related changes that may
drive problems in growth. Similar studies in “closer” animals like mouse are
more difficult. We now use zebrafish to examine bladder growth with advanced
DNA-modifying tools and glowing fish to easily see changes in growth. We have
already created a computer program capable of seeing differences in normal and
abnormal zebrafish bladders. Using the glowing fish, we can see changes more
easily and pick only the fish with problems instead of guessing what may be
wrong just because the fish was in the wrong water. We would like to accomplish
two things. First, we will test whether reported DNA changes after chemical
exposure to understand this affects bladder function. Second, we will put young
zebrafish in water with one of these environmental chemicals, the same way
children would be exposed to chemicals when they are young or if their mothers
drink the water when pregnant, and discover new changes in DNA signals than
change organ function. By doing these experiments, we hope to better understand
the risks of these thousands of chemicals, learn more about urinary organ
growth, and ultimately end these diseases that affect children.